Global economic loss resulting from insect damage to crops is staggering. The economic loss due to damage caused just by Lepidopteran pests in the United States is estimated to be greater than 600 million dollars annually. Accordingly, insecticides are integral components of pest control for modern agriculture. One such insecticide, spinosad, is a mixture of two naturally-occurring metabolites, spinosyn A and spinosyn D, produced by the actinomycete Saccharapolyspora spinosa. Spinosad provides effective control of pests in the insect orders Lepidoptera, Diptera and Thysanoptera, and is also effective against some species of Coleoptera and Orthoptera.
Insecticides such as spinosad generally affect a specific target site, such as a critical protein, within an organism. To date, a limited number of insecticidal target sites have been identified, and many of the insecticides acting at these target sites are losing their effectiveness due to increased resistance in field populations of insects. While spinosad has been used as a naturally-occurring insect control agent, it would be desirable to identify other chemical compounds possessing insecticidal activity that act at the spinosad target site.
Despite various technological advances, the general state of understanding of insecticidal target sites is extremely limited and a need exists for the discovery and development of novel, efficacious and safe insecticides. The present invention addresses this need by providing a novel target site, i.e., the spinosad target site, which is useful for the identification and characterization of new chemistries acting in a manner similar to spinosad and its chemical constituents. In addition, nicotinic acetylcholine receptors from vertebrate species are important target sites for pharmaceutical and animal health compounds that intervene in a number of disease states. Therefore, the present invention also provides a model system for studying nicotinic acetylcholine receptor subunit interactions and pharmacology.